Use of the dTAG system in vivo to degrade CDK2 and CDK5 in adult mice and explore potential safety liabilities.

The degradation tag (dTAG) system for target protein degradation can remove proteins from biological systems without the drawbacks of some genetic methods, such as slow kinetics, lack of reversibility, low specificity, and the inability to titrate dosage. These drawbacks can make it difficult to compare toxicity resulting from genetic and pharmacological interventions, especially in vivo. Because the dTAG system has not been studied extensively in vivo, we explored the use of this system to study the physiological sequalae resulting from CDK2 or CDK5 degradation in adult mice. Mice with homozygous knock-in of the dTAG sequence onto CDK2 and CDK5 were born at Mendelian ratios despite decreased CDK2 or CDK5 protein levels in comparison with wild-type mice. In bone marrow cells and duodenum organoids derived from these mice, treatment with the dTAG degrader dTAG-13 resulted in rapid and robust protein degradation but caused no appreciable change in viability or the transcriptome. Repeated delivery of dTAG-13 in vivo for toxicity studies proved challenging; we explored multiple formulations in an effort to maximize degradation while minimizing formulation-related toxicity. Degradation of CDK2 or CDK5 in all organs except the brain, where dTAG-13 likely did not cross the blood brain barrier, only caused microscopic changes in the testis of CDK2dTAG mice. These findings were corroborated with conditional CDK2 knockout in adult mice. Our results suggest that the dTAG system can provide robust protein degradation in vivo and that loss of CDK2 or CDK5 in adult mice causes no previously unknown phenotypes.

Risk of pediatric inflammatory multi-system syndrome (PIMS or MIS-C) in pediatric patients with COVID-19 presenting with gastrointestinal symptoms.

Introduction and objectives: Pediatric inflammatory multisystem syndrome (PIMS) is a life-threatening complication in pediatric patients with SARS-CoV-2 infection. An increase in the association of gastrointestinal symptoms and the presence of PIMS has been observed. The objective of this study was to analyze whether pediatric patients with COVID-19, who debut with gastrointestinal symptoms, have a higher risk of developing PIMS. Material and methods: An observational, analytical and retrolective study was carried out with a review of the records of patients diagnosed with COVID-19. Demographic, clinical and laboratory variables were recorded. Results: A total of 248 patients who met the selection criteria were included. Of Those 40% were female, with a mean age of 7 +/- 5.8 years. Gastrointestinal symptoms were the initial presentation in 103 patients, with vomiting being the most frequent symptom, followed by abdominal pain and diarrhea. In total 52 patients developed PIMS, 30 of whom presented with gastrointestinal symptoms. A RR of 1.57 (97% CI of 1.17-2.11) was found for the presentation of PIMS in patients positive for SARS-CoV-2 who present with gastrointestinal symptoms. Conclusions: There is an increased risk of developing pediatric multisystem inflammatory syndrome when there are gastrointestinal symptoms in pediatric patients with COVID-19.

Allowing access to parents/caregivers into COVID-19 hospitalization areas does not increase infections among health personnel in a pediatric hospital.

Background: At the beginning of the current COVID-19 pandemic, it became critical to isolate all infected patients, regardless of their age. Isolating children has a negative effect on both, them and their parents/caregivers. Nevertheless isolation was mandatory because of the potential risk that visitation might have on COVID-19 dissemination mostly among health personnel. Methods: From the starting of the COVID-19 pandemic in our pediatric hospital visits were forbidden. This 2 months period (April-May) was called P1. In June parents were allowed to visit (P2), under a visiting protocol previously published. Hospital workers were monitored for the presence of COVID-19 symptoms and tested for the infection when clinically justified. The positivity proportion and the relative risk (RR) of COVID-19 among the health personnel between periods were calculated. The caregivers were also followed up by phone calls. Results: Since April 2020 to November 2020, 2,884 health personnel were studied for 234 days, (318,146 workers days). Although the COVID-19/1,000 health personnel days rate decreased from one period to another (1.43 vs 1.23), no statistically significant differences were found. During P1, 16 patients with COVID-19 were treated. During the follow up none of the family members were infected/symptomatic in P1, while in P2, 6/129 (4.65%) were symptomatic or had a positive test. All of them initiated between 2 and 4 days after the patient's admission. As they also had some other infected family members it was not possible to ensure the source of infection. There were no statistically significant differences in the RR of COVID-19 in health personnel, (RR 1, 95% CI 0.69-1.06, p = 0.162). Conclusions: When safely implemented, allowing parents/caregivers to spend time with their hospitalized COVID-19 children does not increase the contagion risk for hospital workers or among themselves.

Risk Factors of Infection, Hospitalization and Death from SARS-CoV-2: A Population-Based Cohort Study.

We conducted a prospective population-based cohort study to assess risk factors for infection, hospitalization, and death from SARS-CoV-2. The study comprised the people covered by the Health Service of Navarre, Spain. Sociodemographic variables and chronic conditions were obtained from electronic healthcare databases. Confirmed infections, hospitalizations, and deaths from SARS-CoV-2 were obtained from the enhanced epidemiological surveillance during the second SARS-CoV-2 epidemic surge (July-December 2020), in which diagnostic tests were widely available. Among 643,757 people, 5497 confirmed infections, 323 hospitalizations, 38 intensive care unit admissions, and 72 deaths from SARS-CoV-2 per 100,000 inhabitants were observed. A higher incidence of confirmed infection was associated with people aged 15-29 years, nursing home residents, healthcare workers, people born in Latin America or Africa, as well as in those diagnosed with diabetes, cardiovascular disease, chronic obstructive pulmonary disease (COPD), chronic kidney disease, dementia, severe obesity, hypertension and functional dependence. The risk of hospitalization in the population was associated with males, higher age, nursing home residents, Latin American or African origin, and those diagnosed with immunodeficiency, diabetes, cardiovascular disease, COPD, asthma, kidney disease, cerebrovascular disease, cirrhosis, dementia, severe obesity, hypertension and functional dependence. The risk of death was associated with males, higher age, nursing home residents, Latin American origin, low income level, immunodeficiency, diabetes, cardiovascular disease, COPD, kidney disease, dementia, and functional dependence. This study supports the prioritization of the older population, nursing home residents, and people with chronic conditions and functional dependence for SARS-CoV-2 prevention and vaccination, and highlights the need for additional preventive support for immigrants.

Pigeons and the Ambiguous-Cue Problem: A Riddle that Remains Unsolved.

The ambiguous-cue task is composed of two-choice simultaneous discriminations involving three stimuli: positive (P), ambiguous (A), and negative (N). Two different trial types are presented: PA and NA. The ambiguous cue (A) served as an S- in PA trials, but as an S+ in NA trials. When using this procedure, it is typical to observe a less accurate performance in PA trials than in NA trials. This is called the ambiguous-cue effect. Recently, it was reported in starlings that the ambiguous-cue effect decreases when the stimuli are presented on an angled (120°) panel. The hypothesis is that the angled panel facilitates that the two cues from each discrimination are perceived as a compound, precluding value transfer via a second-order conditioning mechanism. In this experiment, we used pigeons and a flat panel. Nevertheless, our data were quite similar to the previous data in starlings. We conclude that the form of the panel cannot explain the ambiguous-cue effect. Several alternatives to be explored in future experiments are suggested. The riddle of the ambiguous-cue problem still remains unsolved.

Modelo anatómico de los plexos cervical y braquial por técnica de engomado y modelaje tridimensional / Anatomical model of the cervical and brachial plexuses by gluing technique and three-dimensional modeling

RESUMEN Fundamento: las preparaciones anatómicas del sistema nervioso periférico son de difícil obtención por la falta de material anatómico apropiado y por la necesidad de aplicar técnicas de conservación no siempre disponibles; lo que justifica la creación de modelos con técnicas simples que permitan mostrar al estudiante las características morfológicas con el mayor nivel de veracidad. Objetivo: describir el proceso de elaboración de un modelo anatómico artesanal de la anatomía macroscópica de los plexos cervical y braquial para el proceso enseñanza aprendizaje. Métodos: se realizó un estudio observacional descriptivo en la Universidad de Ciencias Médicas de Villa Clara en el período enero-diciembre del 2020, con el empleo de métodos teóricos: analítico-sintético, inducción-deducción y enfoque sistémico; y empíricos, la revisión y análisis de la literatura científica y observación participativa. Resultados: la información obtenida permitió la sistematización de las técnicas y procedimientos de elaboración de un modelo anatómico artesanal como medio de enseñanza, en el que se representa de forma objetiva y detallada la constitución y topografía de los plexos cervical y braquial, las relaciones entre ellos y con los nervios craneales vago, accesorio e hipogloso. Conclusiones: se describió la creación de modelos anatómicos artesanales de formaciones anatómicas específicas del sistema nervioso periférico con fines docentes, con materiales de fácil obtención y de bajo costo. El proceso de modelación de los plexos cervical y braquial resultó un ejercicio para profesores y estudiantes que vincula vocación, ciencia y arte, con contribuciones evidentes en la calidad del proceso enseñanza aprendizaje.

ABSTRACT Background: anatomical preparations of the peripheral nervous system are difficult to obtain due to the lack of appropriate anatomical material and the need to apply conservation techniques that are not always available; which justifies the creation of models with simple techniques that allow the student to show the morphological characteristics with the highest level of accuracy. Objective: to describe the process of elaboration of a handcraft anatomical model of the macroscopic anatomy of the cervical and brachial plexuses for the teaching-learning process. Methods: a descriptive observational study was carried out at the Villa Clara University of Medical Sciences from January to December 2020, using theoretical methods: analytical-synthetic, induction-deduction and systemic approach; and empirical ones, the review and analysis of scientific literature and participatory observation. Results: the information obtained allowed the systematization of the techniques and procedures for the elaboration of a handcraft anatomical model a teaching aid, in which the constitution and topography of the cervical and brachial plexuses, the relationships between them, are represented objectively and in detail with the vagus, accessory, and hypoglossal cranial nerves. Conclusions: the creation of handmade anatomical models of specific anatomical formations of the peripheral nervous system for teaching purposes, with easily obtained and low-cost materials, was described. The process of modeling the cervical and brachial plexuses was an exercise for teachers and students that link vocation, science and art, with obvious contributions to the quality of the teaching-learning process.

Cómo perciben los niños el jaguar, Panthera onca (Carnivora: Felidae) en Jalisco, México

Los estudios sobre percepción humana hacia depredadores, generalmente se realizan con adultos. Sin embargo, es importante entender las percepciones de los niños, para diseñar estrategias de conservación y educación ambiental efectivas a largo plazo, ya que muchos de ellos serán los futuros manejadores de los recursos naturales. Analizamos las percepciones sobre el jaguar en niños de 8-12 años (n = 89) en comunidades dentro de la Reserva de la Biosfera Sierra de Manantlán (RBSM) y en su zona de influencia (ZI). Para conocer la percepción del jaguar, organizamos talleres con los niños, guiándolos con preguntas abiertas que respondieron con dibujos: ¿Qué animales viven en el monte/bosque? ¿Qué animales peligrosos viven en el monte/bosque? ¿Cómo es el jaguar y qué come? En todas las preguntas se especificó que nos referíamos a los animales presentes en los alrededores de su comunidad. Aparentemente el miedo colectivo hacia los animales influye en que animales se perciben en el entorno, ya que casi nadie dibujó al jaguar como parte del paisaje, pero si como animal peligroso. Las serpientes fueron las que más se relacionan como parte del entorno, y a la vez fueron las que más se mencionaron como animales peligrosos en ambas zonas. En el dibujo de animales peligrosos, hubo 72 menciones de animales no nativos. En ambas áreas, poco más de la mitad de los niños reconoce la forma básica del jaguar. Sobre todo, en la RBSM, la mayoría dibujó ganado vacuno en la dieta del jaguar, representando uno de los conflictos jaguar-humanos. Casi la mitad de los niños dibujó a los venados como parte de la dieta del jaguar en la RBSM y un tercio en la ZI. Un número considerable de niños incluyeron humanos en la dieta en ambas zonas. Concluimos que con el fin de mejorar la percepción es deseable desarrollar estrategias para cambiar las percepciones negativas del jaguar. Por ende, es importante generar material educativo y llevar a cabo campañas de educación ambiental resaltando la importancia ecológica del jaguar, enfatizando que el buen manejo del ganado reduce la depredación y que los humanos no son elementos de la dieta del jaguar. En resumen, es importante generar mayor empatía con el jaguar, y aclarar creencias erradas que puedan afectar la supervivencia del jaguar a largo plazo en estas áreas.

Predator perception studies generally only regard adults. However, it is necessary to also understand children perceptions in order to achieve more effective long term conservation and environmental educational strategies, since many of them will be the future resource managers. We analyze perceptions of the jaguar amongst children (n = 89) between 8 and 12 years old, in the Sierra de Manantlán Biosphere Reserve (SMBR) and its influence zone (ZI). To understand their perceptions, we organized workshops, using open-ended questions, to be answered with drawings: What animals live in the forest? Which dangerous animals live in the forest? What do jaguars look like and what do they eat? In all questions, we specified that we referred to animals close to their community. Apparently collective apprehension influences, which animals are perceived as part of the environment. Our results suggest that the jaguar is not conceived as part of the (direct) environment, but is conceived as dangerous animal in the area. Snakes are most mentioned as part of the environment; at the same time, they are perceived as the most dangerous. In the dangerous animal drawings, there were 72 mentions of no native animals. In all cases, more than half of the children knew the basic shape of a jaguar. Overall in the SMBR, most children drew cattle as the main food staple for the jaguar, representing one of the human-jaguar conflicts. Half of children drew deer as jaguar diet in the SMBR and one third in the ZI. A considerable number of children included humans in the jaguar diet in both zones. We conclude that it is necessary to develop strategies to change the negative perceptions of the jaguar. As such, it is important to generate educational material and carry out educational campaigns that highlight the ecological importance of the jaguar, and emphasizing those livestock management actions to reduce predation and the disappearance of false beliefs; which include jaguar as a people eater. In summary, is important to generate greater empathy with the jaguar, and clarify misconceptions that may affect the long-term survival of the jaguar in these areas.

HGF/c-Met acts as an alternative angiogenic pathway in sunitinib-resistant tumors.

Molecular and cellular mechanisms underlying resistance/low responsiveness to antiangiogenic compounds are under extensive investigations. Both populations of tumor and stroma (nontumor compartment) seem to contribute in inherent/acquired resistance to antiangiogenic therapy. Here, investigating in vivo efficacy of sunitinib in experimental models resulted in the identification of tumors that were resistant/sensitive to the therapy. Analysis of tumor protein lysates indicated a greater concentration of hepatocyte growth factor (HGF) in resistant tumors than in sensitive ones. In addition, using flow cytometry, c-Met expression was found to be significantly higher in endothelial cells than in tumor cells, suggesting that HGF might target the vascular endothelial cells in resistant tumors. Combination of sunitinib and a selective c-Met inhibitor significantly inhibited tumor growth compared with sunitinib or c-Met inhibitor alone in resistant tumors. Histology and in vitro analyses suggested that combination treatment mainly targeted the vasculature in the resistant tumors. Conversely, systemic injection of HGF in the sensitive tumor models conferred resistance to sunitinib through maintenance of tumor angiogenesis. In conclusion, our study indicates a role for HGF/c-Met pathway in development of resistance to antiangiogenic therapy and suggests a potential strategy to circumvent resistance to vascular endothelial growth factor receptor tyrosine kinase inhibitor in the clinic.

Características de las adolescentes obstétricas: estudio comparativo con pacientes de 19 a 30 años del Hospital Universitario de Caldas-1989

Comparamos un grupo de 490 primigestantes primíparas adolescentes, de 18 años de edad o menos, on 471 primigestantes primíparas de 19-30 años. Encontramos dos tipos de diferencias: unas clínica y estadísticaente significativas. Otras sólo clínicamente importantes. En cuanto a las primeras, está la mayor incidencia de unión inestable y de pacientes sin control prenatal entre las adolescentes. La morbilidad gestacional fue mayor entre las adolescentes en unión inestable(p menor 0.05). Hubo también mayor incidencia de amenaza de parto pretérmino (p-0.023) y de sufrimiento fetal (p-0.045) entre las adolescentes que en el subgrupo testigo de 19-24 años. En cuanto a diferencias importantes con significancia clínica no estadística encontramos: mayor incidencia entre las adolescentes, de atonía uterina, sufrimiento fetal intraparto, y parto disfuncional, que en las de 19-24 años y de preeclampsia-eclapmsia , amenaza de parto pretérmino, recién nacido pretérmino, bajo peso para la edad gestacional y RCIU que en el grupo de comparación de 25-30años. La incidencia de preeclampsia-eclampsia en adolescentes primigestantes primíparas fue en nuestro estudio de 9.2 por ciento, 2.2 veces mayor que el promedio de 4.1 por ciento reportado por Pardo-Uriza (2) en su estudio cooperativo de 11 Instituciones Colombianas

Factores de riesgo de infección postcesárea Hospital Universitario de Caldas

En el Hospital Universitario de Caldas, Manizales, Colombia, se adelantó entre el 1 de enero y el 31 de diciembre de 1988, un estudio analítico de casos y controles con el propósito de identificar factores de riesgo de infección postcesárea. Para el efecto, se seleccionaron como casos 50 pacientes infectadas después de cesárea. Como controles se tomaron 573 pacientes que no presentaron infección postcesárea. Se observó asociación estadística entre los casos y las variables "Meconio"(odd ratio:1.9 p-0.04) y "Antibióticos Profilácticos" (odd ratio": 0.29 p-0.002). La presencia de Meconio es factor de riesgo de infección postcesárea. El uso de antibióticos es factor protectivo contra la infección

Correlación entre bacaf y estudio histopatológico: estudio retrospectivo 1989-1995 - Hospital de Caldas

Se revisaron las historias clínicas de 281 pacientes sometidas a biospia aspirativa con aguja fina (BACAF) de la mama, en el período comprometido entre el 1 de julio de 1989 y el 30 de noviembre de 1995. Se seleccionaron 91 casos en los que hubo estudio histológico posterior. La correlación del diagnóstico por BACAF con el diagnóstico histopatológico final condujo a los siguientes resultados: sensibilidad 88.9 por ciento, Especificidad 75.7 por ciento, Valor predictivo de la prueba positiva (VPPP) 84.2 por ciento, Valor predictivo de la prueba negativa (VPPN) 82.3 por ciento.

Tromboembolia pulmonar en autopsias en un periodo de 10 años / Pulmonary thomboemlism in autopsies over 10 years

En 10 años se realizaron 1685 autopsias y se documentó tromboembolia pulmonar en 252 casos (15 por ciento). Se identificó en vida trombosis venosa profunda en 15 y tromboembolia pulmonar en 52. De los confirmados por autopsia, la tromboembolia pulmonar fue causa de la muerte en 71 (28.4 por ciento), un factor coadyuvante en 157 (62 por ciento) e incidental en 24 caos (9.6 por ciento). En méxico, los trabajos de frecuencia de tromboembolia, es recomendable establecer las medidas profilácticas convenientes: uso de medias elásticas, ambulación, ejercicios y heparina convencional o de bajo peso molecular.